論文 - 詳細
| RRC ID | 45321 |
|---|---|
| 著者 | Ogawa F, Amano H, Eshima K, Ito Y, Matsui Y, Hosono K, Kitasato H, Iyoda A, Iwabuchi K, Kumagai Y, Satoh Y, Narumiya S, Majima M. |
| タイトル | Prostanoid induces premetastatic niche in regional lymph nodes. |
| ジャーナル | J Clin Invest |
| Abstract |
The lymphatic system is an important route for cancer dissemination, and lymph node metastasis (LNM) serves as a critical prognostic determinant in cancer patients. We investigated the contribution of COX-2-derived prostaglandin E2 (PGE2) in the formation of a premetastatic niche and LNM. A murine model of Lewis lung carcinoma (LLC) cell metastasis revealed that COX-2 is expressed in DCs from the early stage in the lymph node subcapsular regions, and COX-2 inhibition markedly suppressed mediastinal LNM. Stromal cell-derived factor-1 (SDF-1) was elevated in DCs before LLC cell infiltration to the lymph nodes, and a COX-2 inhibitor, an SDF-1 antagonist, and a CXCR4 neutralizing antibody all reduced LNM. Moreover, LNM was reduced in mice lacking the PGE2 receptor EP3, and stimulation of cultured DCs with an EP3 agonist increased SDF-1 production. Compared with WT CD11c+ DCs, injection of EP3-deficient CD11c+ DCs dramatically reduced accumulation of SDF-1+CD11c+ DCs in regional LNs and LNM in LLC-injected mice. Accumulation of Tregs and lymph node lymphangiogenesis, which may influence the fate of metastasized tumor cells, was also COX-2/EP3-dependent. These results indicate that DCs induce a premetastatic niche during LNM via COX-2/EP3-dependent induction of SDF-1 and suggest that inhibition of this signaling axis may be an effective strategy to suppress premetastatic niche formation and LNM. |
| 巻・号 | 124(11) |
| ページ | 4882-94 |
| 公開日 | 2014-11-1 |
| DOI | 10.1172/JCI73530 |
| PII | 73530 |
| PMID | 25271626 |
| PMC | PMC4347225 |
| MeSH | Animals Antineoplastic Agents / pharmacology Carcinoma, Lewis Lung / immunology Carcinoma, Lewis Lung / metabolism Carcinoma, Lewis Lung / secondary* Celecoxib Cell Line, Tumor Chemokine CXCL12 / metabolism Cyclooxygenase 2 / metabolism Cyclooxygenase 2 Inhibitors / pharmacology Dendritic Cells / immunology Dinoprostone / physiology* Drug Screening Assays, Antitumor Gene Knockout Techniques Lung Neoplasms / immunology Lung Neoplasms / metabolism Lung Neoplasms / pathology* Lymph Nodes / immunology Lymph Nodes / pathology* Lymphangiogenesis Lymphatic Metastasis Male Mice, Knockout Neoplasm Transplantation Pyrazoles / pharmacology Receptors, CXCR4 / metabolism Receptors, Prostaglandin E, EP3 Subtype / genetics Receptors, Prostaglandin E, EP3 Subtype / metabolism Signal Transduction Sulfonamides / pharmacology T-Lymphocytes, Regulatory / immunology |
| IF | 11.864 |
| 引用数 | 37 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LLC(RCB0558) |